WO-A-03/076446 discloses a multitude of C-10-substituted derivatives of dihydroartemisinin of the following formula
in which R1 and R2 may be a wide variety of organic radicals optionally containing heteroatom moieties, X is, for example, S, an S(═O), PR3, P—O—R3 or P—N(R4)—R3 group, with R3 and R4 being in turn organic radicals, and Z is oxygen, sulphur or an NR5 radical, with R5 being in turn an organic radical.
WO-A-00/04024 discloses further C-10-substituted derivatives of dihydroartemisinin of the general formula (1)
where Y is a halogen atom, an optionally substituted cycloalkyl, aryl, a C-bonded heteroaryl or a heterocycloalkyl radical, or is an NR1R2 group where R1 is hydrogen or an optionally substituted alkyl, alkenyl or alkynyl radical and R2 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or aralkyl radical, or else R1 and R2 together with the adjacent nitrogen atom are an optionally substituted heterocyclic group or an amino group derived from an optionally substituted amino acid ester.
Such compounds described in WO-A-03/076446 and WO-A-00/04024 are effective in the treatment of parasitic infections such as malaria, neosporosis or coccidiosis.
Also mentioned in WO-A-00/04024 is 10α-[4′-(S,S-dioxothiomorpholin-1′-yl)]-10-deoxo-10-dihydroartemisinin (1a) as a compound of the general formula (1).

WO-A-00/04024 describes the synthesis of the compounds of the general formula (1) by reacting a dihydroartemisinin of the formula (2)
where Q is a hydrogen atom or a trimethylsilyl group with a halogenating agent to form a compound of the formula (1) in which Y is a halogen atom, and subsequently reacting with a Grignard of the formula YMgX where X=halogen or with an amine of the general formula HNR1R2.
The preparation of 10α-[4′-(S,S-dioxothiomorpholin-1′-yl)]-10-deoxo-10-dihydroartemisinin (1a) is described in WO-A-00/04024 starting from dihydroartemisinin of the formula (2a) and thiomorpholine of the formula (3). According to Examples 3(a), 3(b), 6 and 7, dihydroartemisinin (2a) is reacted first with chlorotrimethylsilane and then with bromotrimethylsilane, and then 3 equivalents of thiomorpholine are added to form the compound of the formula (4). This compound of the formula (4) is isolated as an intermediate. Both reactions are effected at very low temperatures in the region of 0° C. and room temperature. The subsequent oxidation of the compound of the formula (4) affords the target compound of the formula (1a), NMO meaning 4-methylmorpholine N-oxide and TPAP=tetrapropylammonium perruthenate.

A disadvantage of this synthesis is that it is a two-stage process and 3 equivalents of the expensive thiomorpholine feedstock have to be used.
It is thus an object of the present invention to provide an improved process for preparing 10α-[4′-(S,S-dioxothiomorpholin-1′-yl)]-10-deoxo-10-dihydroartemisinin (1a).